The goal of this work is to apply the approaches and methodologies of modern molecular biology to the problem of gene expression in malaria parasites. The malaria parasite is interesting both as a basic developmental biological system and because of its major relevance as a world health problem. By a basic analysis of gene expression in the malaria parasite and the identification of developmentally regulated genes, I hope both to understand gene regulation in the parasite life cycle and to identify relevant disease related antigens. The malaria parasite (Plasmodium sp) is a protozoan that develops through a complex life cycle involving both intracellular and extracellular forms, haploid and diploid stages and passage through insect vectors and vertebrate hosts, yet has a genetic complexity only five times that of bacteria. There are at least four distinct forms of the malaria parasite during the course of its life cycle, two within its insect vector and two within its vertebrate host. Each of these forms is both functionally and morphologically distinct from the others, reflecting the expression of specific distinct genes at each stage. Not only must these genes be expressed in a precise manner, but each organism must retain the ability to re-express the same specific genes at precisely the same time in the next life cycle. Initially, I will focus on the sexual and subsequent diploid stages of malaria parasite life cycle within the insect vector. I chose this segment of the life cycle because gametogenesis, zygote formation and subsequent ookinete development are well characterized biologically and can be studied in an in vitro system. In addition, gametes and fertilized zygotes are the targets of transmission-blocking immunity in malaria and it may be possible to identify and clone those parasite genes encoding relevant transmission-blocking antigens. Such cloned genes could be used for the production of a safe and effective transmission-blocking vaccine. The eventual aim of this work is to identify and clone gamete specific genes encoding developmentally regulated proteins using recombinant DNA technology. These cloned genes will be used to study gene structure and genome organization and to analyze gene regulation at the transcriptional level.